Plasma bicarbonate losses during acetate dialysis were prevented by using a combination of acetate and bicarbonate in the dialysate. In 21 patients who were treated with combination dialysate, the fall in mean blood pressure (MBP), and frequency of symptoms, and post-dialysis task performance were all similar to that observed during dialysis with acetate alone. Furthermore, dialysis performed with bicarbonate dialysate resulted in significantly smaller MBP drops, fewer symptoms, and an improved task performance compared to either an acetate or a combination dialysis. These findings indicate that the presence of acetate, rather than a bicarbonate loss, was responsible for the patients' intolerance to acetate dialysis. Patients symptomatic on acetate dialysis had a similar ultrafiltration rate, weight loss, MBP drops, and postdialysis serum acetate levels; they were similar in age and weight to symptom-free patients. Thus, the toxic effect of acetate was not related to serum acetate level. There was no difference in bicarbonate dialysis between patients with symptoms on acetate and the symptom-free patients in reference to MBP drops and task performance. This finding suggests that symptomatic patients were not simply less tolerant to the process of dialysis, but differed from symptom-free patients in their response to the presence of acetate.